Crystalline derivatives preparation

McDonald and Jackson141 prepared liquid 6-methyl-D-fructose [a]D +6.4° in water, by the following reaction sequence di-D-fructose anhydride I — 6,6 -ditrityl-di-D-fructose anhydride I —> 6,6 -ditrityl-di-D-fructose anhydride I 3,4,3, 4 -tetraacetate — di-D-fructose anhydride I 3,4,3, 4 -tetraacetate — 6,6 -dimethyl-di-D-fructose anhydride I 3,4,3, -4 -tetraacetate — 6,6 -dimethyl-di-D-fructose anhydride I — 6-methyl-D-fructose. The possibility of acetyl migration during methylation makes it dangerous to rely on this synthesis as a definitive one for 6-methyl-D-fructose, especially as the proof of structure depends largely on the method of formation. The only crystalline derivative prepared by... 

A crystalline derivative of benzyl alcohol cannot be obtained by using benzoyl chloride, because the benzyl benzoate, C HiCOOCHiCaHj, so obtained has m.p. 18°, and is thus usually liquid the present preparation illustrates therefore the use of a substituted benzoyl chloride (p-nitrobenzoyl chloride, m.p. 75°) in order to obtain a crystalline derivative of suitably high m.p. 

In eachof the Sections 10-27, the chief physical propertiesof the compounds concerned are Erst briefly indicated a list of the gen eral reactionsf is then given, followed by practical directions for the application or illustration of these general reactions. The types of crystalline derivatives which can be most readily and reliably prepared are then given, with practical examples. Finally, any important special reactions of individual members are described. 

Aliphatic and aromatic acids, simple and substituted, vary con siderably in their properties, and no one reaction for the preparation of crystalline derivatives is general. The following are recommended as most promising. 

Aqueous solutions give with ferric chloride the characteristic reactions of the neutral salt of the acid (p. 348). Identify the carboxylic acids by the tests already given (Section 14, p. 347), or by the preparation of one of the crystalline derivatives below. 

D) No general reaction can be cited for the preparation of crystalline derivatives of Class (iii). Triphenylamine, when nitrated in acetic acid with fuming nitric acid, gives tri-/>-nitrophenylamine, m.p. 280°. The presence of substituents in the phenyl groups may however complicate or invalidate nitration. 

These are not essential if the acid and amine obtained on hydrolysis are crystalline but crystalline derivatives of the acid and amine can be prepared by the standard methods for acids (p. 349) and amines (pp. 374, 376) respectively. 

First, considerably greater emphasis has been placed on semimicro techniques and their application to preparations, separations, analysis and physical determinations such as those of molecular weight. We have therefore greatly expanded the section on Manipulation on a semi-micro scale which was in the Third Edition, and we have described many more preparations on this scale, some independent and others as alternatives to the larger-scale preparations which immediately precede them. Some 40 separate preparations on the semi-micro scale are described in detail, in addition to specific directions for the preparation of many classes of crystalline derivatives required for identification purposes. The equipment required for these small-scale reactions has been selected on a realistic basis, and care has been taken not to include the very curious pieces of apparatus sometimes suggested as necessary for working on the semi-micro scale. 

In Part III, dealing with the Reactions and Identification of Organic Compounds, greater emphasis has now been placed on the preparation of suitable crystalline derivatives. Quite apart from the importance of these derivatives for purposes of identification, encouragement is thereby given to the student to gain experience in small-scale preparative work. 

Because of the chemical inertness of the paraffin hydrocarbons and of the closely related cycZoparaffins, no satisfactory crystalline derivatives can be prepared. Reliance is therefore placed upon the physical properties (boding point, density, and refractive index) of the redistilled samples. These are collected together in Table III,6. 

Triiodobenzoates. The derivatives enumerated above are unsatisfactory for alcohol - ethers, e.g., the mono-ethers of ethyleneglycol ( cellosolves ) and the mono-ethers of diethyleneglycol ( car-bitols ) (see Table 111,27). Crystalline derivatives of alcohol - ethers are readily obtained with 3 4 5-triiodobenzoyl chloride (for preparation, see Section VII,21), for example ... 

The low reactivity of aliphatic ethers renders the problem of the preparation of suitable crystalline derivatives a somewhat difficult one. Increased importance is therefore attached to the physical properties (boding point, density and refractive index) as a means for providing preliminary information. There are, however, two reactions based upon the cleavage of the ethers which are useful for characterisation. 

Reflux 1 ml. of the ether with 5 ml. of freshly distilled, constant boiling point hydriodic acid (Section 11,49,2), b.p. 126-128°, for 2-3 hours. Add 10 ml. of water, distil and collect about 7 ml. of liquid. Decolourise the distillate by the addition of a httle sodium bisulphite, and separate the two layers by means of a dropper pipette (Fig. 11,27,1). Determine the b.p. of the resulting iodide by the Siwoloboff method (Section 11,12) and prepare a crystalline derivative (Section 111,42). 

Crystalline derivatives may be prepared with xanthhydrol (9-hydroxy-xanthen), but the reagent is comparatively, expensive. Xanthhydrol reacts with primary amide,s with the formation of crystalline xanthyl-amides or 9-acylamidoxanthens ... 

The above reactions wiU serve to place an amine into its class— primary, secondary or tertiary. For complete characterisation, a crystalline derivative should be prepared. A large number of derivatives of amines are avaUable the foUowing wiU be found useful. 

Crystalline derivatives, suitable for identification and characterisation are dealt with in Section IV, 114, but the preparation of the following, largely liquid, derivatives will be described in the following Sections. When phenols are dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, they undergo rapid and almost quantitative acetylation if the temperature is kept low throughout the reaction. This is because phenols form readily soluble sodium derivatives, which react with acetic anhydride before the latter undergoes appreciable hydrolysis, for example ... 

The characterisation of a primary aromatic amide is based upon its own m.p. and the identification of the acid (see Section IV,175) produced on hydrolysis. A crystalline derivative may be prepared directly with xanthhydrol (for experimental details, see Section 111,110, 1). 

The above reagent is very dilute and is intended for qualitative reactions. It is hardly suitable for the preparation of crystalline derivatives except in very small quantities (compare Section 111,74,7). 

Benzamidomethyl-A -methylcysteine has been prepared as a crystalline derivative (H0CH2NHC0C6H 5, anhydr. CF3CO2H, 25°, 45 min, 88% yield as the tri-fluoroacetate salt) and cleaved (100% yield) by treatment with mercury(II) acetate (pH 4, 25°, 1 h) followed by hydrogen sulfide. Attempted preparation of S-acetamidomethyl-N-methylcysteine resulted in noncrystalline material, shown by TLC to be a mixture. ... 

From l-cyclohexyl-3-ethyldiaziridine, crystalline derivatives have been prepared with p-toluenesulfonyl chloride and with 3,5-dinitro-benzoyl chloride, e.g., 46/ The quantitative liberation of iodine from acid iodide solution characterizes these compounds as true diaziridines. 

It is a doubly unsaturated bicyclic sesquiterpene from which no crystalline derivatives have, so far, heen prepared. 

The identification of citral is a matter of considerable importance, and may be effected by the preparation of several well-defined crystalline derivatives. 

Imine formation from such reagents as hydroxylamine and 2,4-dinitro-phenylhydrazine is sometimes useful because the products of these reactions— oximes and 2,4-dinitrophenylhydrazones (2,4-DNPs), respectively—are often crystalline and easy to handle. Such crystalline derivatives are occasionally prepared as a means of purifying and characterizing liquid ketones or aldehydes. 

The residue in the flask will contain the sodium (or potassium) salt of the acid together with excess of alkali. Just acidify with dilute sulphuric arid and observe whether a crystalline acid separates if it does, filter, recrystallise and identify (Section 111,85). If no crystalline solid is obtained, the solution may be just neutralised to phenolphthalein and the solution of the alkali salt used for the preparation of a crystalline derivative. This will confirm, if necessary, the results of hydrolysis by method 1. If the time factor is important, either method 1 or the product of the caustic alkali hydrolysis may be used for the identification of the acid. 

The preparation of crystalline derivatives, including 2 4-dinitro-phenyl hydrazones, semicarbazones, oximes, phenylhydrazones and p-nitrophenylhydrazones can be carried out as described under Aromatic Aldehydes, Section IV,135. 

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